Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
School of Environmental Science and Engineering, Hainan University, China.
Environ Int. 2024 Aug;190:108872. doi: 10.1016/j.envint.2024.108872. Epub 2024 Jul 4.
Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear.
We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm).
This study included 285 mother-child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm.
Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05).
Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.
研究发现，接触内分泌干扰化学物质（EDCs）与儿童生长和发育异常有关。然而，怀孕期间接触 EDCs 增加儿童肥胖风险的潜在机制仍不清楚。
我们旨在探讨产前 EDC 暴露与儿童两岁时的体重指数（BMI）之间的关联，并进一步探讨 DNA 甲基化（DNAm）的潜在影响。
本研究纳入了来自中国武汉出生队列的 285 对母婴。在大约 24 个月龄时评估每个儿童的 BMI。使用超高效液相色谱-三重四极杆质谱联用仪测量妊娠第 1、2 和 3 期的 16 种 EDC 浓度。使用广义线性模型、加权分位数和贝叶斯核机器回归评估产前 EDC 暴露与儿童 BMIz 之间的关联。使用 Human Methylation EPIC BeadChip 阵列测量脐带血 DNAm。使用稳健线性模型进行与 BMIz 相关的全基因组 DNAm 关联研究。然后进行中介分析以探索 DNAm 的潜在中介。
7 种 EDC 的尿液浓度与第 1 期 BMIz 呈正相关，在 WQS 模型中仍具有统计学意义。共有 641 个差异 DNAm 位置与升高的 BMIz 相关。12 个 CpG 位置（注释为 DUXA、TMEM132C、SEC13、ID4、GRM4、C2CD2、PRAC1&PRAC2、TSPAN6 和 DNAH10）介导了尿液 BP-3/BPS/MEP/TCS 与升高的 BMIz 之间的关联（P<0.05）。
我们的结果表明，产前接触 EDCs 与儿童肥胖风险增加有关，特定的 DNAm 作为部分中介。
